AMPHOTERICIN Â CHANNEL CONDUCTANCE INACTIVATION
V. Kh. Ibragimova,1 I. N. Aliyeva,2 D. I. Aliyev 2
1 Institute of Radiation Problems, National Academy of Sciences of Azerbaijan Republic, Baku, and
2 Deparment of Biophysics, Baku State University, Azerbaijan Republic;
2 e-mail: dshaliev@hotmail.com
Effects induced in bilayer lipid membranes by amphotericin  and its alkyl derivatives was analysed. Inactivation of the antibiotic-dependent multichannel
membrane conductance was discovered. Kinetics of membrane conductivity was shown to depend on the antibiotic concentration in the membrane. At concentrations between
10-8-10-7 M, the resulting conductance appeared to the transient. We suggest that the phenomenon of biphasic kinetics of membrane conductance
is the result of a consecutive transformation of polyene channels in the membrane: half-pores are assembled on either side of membrane-nonconducting 1; two half-pores
combine to build up a conducting channels-conducting 2, and the conducting channels are dissassemled to monomeres and nonconducting self-associated forms inside the
membrane-disassembled state (nonconducting 3). To explain the transient characteristics of the induced conductance, it is proposed that the antibiotic, present in the solution
under self-associated form, binds the membrane and forms pores, then dissociates in the bilayer in a non-active monomeric form. The existence of definite monomers and
nonconducting self-associated forms of amphotericin  molecules inside the membrane was estimated from the dependence of kinetic conductance of lipid membranes of
amphotericin  and its alkyl derivatives, when the antibiotics are washed out from aqueous medium. Equilibrium between different antibiotic assemblies inside the membrane
was demonstrated by the kinetics of conductance decrease following washing the antibiotic. Using circular dichroism measurements, we observed that amphotericin  alkyl
derivatives were in self-associated form being susceptible to form pores across cholesterol-containing membranes. The phenomenon of biophasic kinetics was observed only in
the cholesterol-containing membrane. The substitution of membrane cholesterol for ergosterol provides monotonic kinetics of membrane conductance at any antibiotic
concentration.
Key words: amphotericin B, alkyl derivatives, lipid membranes, channels, membrane conductivity, circular dichroism
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